Insulin Degludec Research Articles

The Clinical Impact of Switching Basal Insulin to Insulin Degludec in Patients With Diabetes in Saudi Arabia: A Retrospective One-Group Pretest-Posttest Design Study.

Diabetes is a health problem that has an enormous and intolerable public health burden on the individual, family, and community. Diabetes affects nearly one-fifth of adults in Saudi Arabia and is expected to double by 2030. The study aims to evaluate the impact of switching patients from conventional basal insulin analogues to insulin degludec during a 90-day follow-up period. This was a retrospective observational pretest-posttest cohort study conducted at King Abdulaziz University Hospital between June 2019 and August 2020. Adult patients with diabetes who switched their basal insulin to insulin degludec were included and evaluated for its impact on insulin doses, hemoglobin A1c (HbA1c), hypoglycemic events, and/or body weight changes during a 90-day follow-up period. Out of 718 patients, 107 patients were included in the study, with 60.7% being females and their mean (± SD) age was 62.2 ± 14.6 years. There was a significant decrease in the mean baseline of HbA1c from 9.2% to 8.7% after 90 days of follow-up (P<0.001). A statistically significant reduction was noted in the total insulin requirements from a baseline of 71.70 (± 42.4) units to 46.5 (± 29) units, P=0.001, after switching to insulin degludec. However, there were no statistically significant differences in the body weight from the baseline mean (± SD) of 80.5 kg (± 19.4) to 79.9 kg (± 19.9), P=0.68, after switching to insulin degludec. Lastly, there were no statistically significant differences in the reported hypoglycemic episodes from a baseline of 48.7% vs 37.3% after 90 days of follow-up (P = 0.166). Switching to the novel insulin degludec conferred better blood glucose control and dose reduction. There was no increase in the frequency of hypoglycemic episodes or body weight.

Efficacy and Safety of Tirzepatide in Type 2 Diabetes: The Surpass Clinical Trial Program

Tirzepatide is a novel, once-weekly, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is approved for the treatment of type 2 diabetes (T2D). The efficacy and safety of tirzepatide has been assessed in five Phase 3 trials from the SURPASS program in a broad T2D population across the treatment continuum. The objective of this review is to summarize the results from the completed trials. At primary endpoints of 40 and 52 weeks, tirzepatide 5, 10, and 15 mg demonstrated superiority in reductions from baseline in glycated hemoglobin (HbA1c) and body weight versus placebo (SURPASS-1 monotherapy and SURPASS-5 add-on to basal insulin), versus semaglutide 1 mg (SURPASS-2 add-on to metformin), versus insulin degludec (SURPASS-3 add on to metformin ± sodium glucose cotransporter 2 inhibitor [SGLT2i]), and versus insulin glargine (SURPASS-4 add-on to metformin ± sulfonylurea ± SGLT2i]). A greater proportion of tirzepatide-treated participants reached HbA1c targets of <7.0%, ≤6.5% and <5.7% (i.e., normoglycemia) without increased risk in clinically significant hypoglycemia (blood glucose <54 mg/dL). Adding tirzepatide to basal insulin decreased the total daily insulin dosage. The overall safety profile of tirzepatide was similar to that of the GLP-1 receptor agonist class. The most common adverse events were gastrointestinal, mostly mild to moderate in severity, transient, and decreased over time. Given the unprecedented reduction in HbA1c and body weight without increased risk of hypoglycemia in various populations along the spectrum of diabetes care, tirzepatide demonstrated potential as first-line therapy for T2D treatment.

Pragmatic use of insulin degludec/insulin aspart co-formulation: A multinational consensus statement.

Insulin degludec/insulin aspart (IDegAsp) is a modern coformulation of ultra-long-acting basal insulin degludec, with rapid-acting insulin aspart. IDegAsp provides effective, safe, well-tolerated glycemic control, with a low risk of hypoglycemia while allowing flexibility in meal patterns and timing of administration. This consensus statement describes a pragmatic framework to identify patients who may benefit from IDegAsp therapy. It highlights the utility of IDegAsp in type 2 diabetic patients who are insulin-naive, suboptimally controlled on basal or premixed insulin, or dissatisfied with basal–bolus regimens. It also describes potential IDegAsp usage in type 1 diabetic patients.

Comparative assessment of modern parameters of glycemic control in children with type 1 diabetes after switching to fast-acting insulin aspart using Flash Glucose Monitoring in real clinical practice

BACKGROUND: Postprandial hyperglycaemia contributes significantly to the lack of glycaemic control in patients with type 1 diabetes mellitus (DM1). At least a quarter of patients forget to inject insulin before meals once a week, and more than 40% of them inject bolus insulin immediately before meals, which does not correspond to the pharmacokinetic effects of ultrashort insulins and determines the need to use insulins with better imitations of physiological insulin secretion.AIM: To assess the effect of fast acting insulin aspart (FIAsp) on the current parameters of glycaemic control in children with DM1 after switching from insulin Asp (iAsp) using continuous glucose monitoring.MATERIALS AND METHODS: A multicenter observational 12-week prospective open-label uncontrolled comparative study was initiated. A group of insufficiently controlled patients were identified (n = 48) including a group on multiple insulin injections therapy (MII) (insulin degludec and IAsp) and a group on continuous subcutaneous insulin infusion (CSII) of iAsp. Three 14-day flash glucose monitoring (FMG) were performed: before transferring patients to FiAsp and after 2 and 12 weeks of the transfer. Key endpoints: HbA1c after 2 and 12 weeks on FiAsp relative to baseline, analysis of 5 FMG target glucose ranges, presented as an ambulatory glycemic profile. Additional indicators: dynamics of insulin daily dose, frequency of glucose self- monitoring, the number of severe hypoglycemia, adverse events that occurred during treatment.RESULTS: 2 weeks after the transfer from IAsp to FIAsp, TIR increased in the entire group of patients: from 53% [44.3; 66.5] to 57% [47.4; 71.0] (p-value = 0.010) and TAR decreased from 38% [24.8; 50.2] to 30.5% [22.0; 45, 0] (p-value = 0.0124). Maintaining and increase time spent in the target glucose ranges during a 12-week observation period, in parallel with a significant decrease in hypoglycemic episodes &lt;3.9 mmol / L per week, on FIAsp therapy naturally leads to an improvement in diabetes control: a decrease in HbA1c from 8.15% up to 7.75% (p-value = 0.0224), more pronounced in the group of patients on CSII — from 7.9% to 7.5% (p-value = 0.028).CONCLUSION: Switching from IAsp to BDIAsp in routine clinical practice in the MII and CSII regimen in children and adolescents with type 1 diabetes allows achieving better glycemic control compared to the previous generation prandial insulin analog Iasp. The better diabetes control is associated with an increase or a trend towards an increase in TIR and a decrease or a trend towards a decrease in TAR and TBR, as well as a significant decrease in episodes of hypoglycemia.

Insulin degludec/liraglutide versus its monotherapy on T2D patients: A lifetime cost-utility analysis in China.

Introduction: IDegLira (brand name Xultophy) is a novel fixed ratio combination of insulin degludec and liraglutide for type 2 diabetes (T2D) patients. This study aimed to investigate the lifetime cost-effective value of IDegLira compared with its single component (Degludec or Liraglutide) and to explore the suitable annual cost of IDegLira if necessary. Methods: UKPDS OM2 was applied to determine the long-term quality-adjusted life years (QALYs) and total costs. The efficacy data that were inputted into the model were synthesized from 6 randomized clinical trials (RCTs) that directly assessed the clinical benefit of IDegLira and its components in the treatment of uncontrolled T2D patients. The economic results were examined by one-way sensitivity analysis (OSA) and probabilistic sensitivity analysis (PSA). Further price reduction of IDegLira was investigated by binary search. Results: The IDegLira, IDeg, and Lira yielded 11.79 QALYs, 11.62 QALYs, and 11.73 QALYs and total cost of $20281.61, $3726.76, and $11941.26, respectively. The incremental cost-utility ratio (ICUR) of IDegLira versus IDeg was $99464.12/QALYs, and the ICUR of IDegLira versus Lira was $143348.26/QALYs, which indicated that IDegLira was not a cost-effective therapy for T2D patients compared with its components at the current price from a Chinese national healthcare system perspective. Base case results were robust to OSA and PSA. A further binary search showed that IDegLira appears to only be cost-effective if the annual cost of IDegLira is decreased by 58% when IDeg is considered as a reference, or by 30.57% when Lira is considered as a reference. Conclusion: In conclusion, IDegLira appears to not be cost-effective when compared with the current prices of IDeg or Lira for T2D patients in China. However, after the binary search, IDegLira appears to only be cost-effective if the annual cost of IDegLira is decreased 58% when IDeg is considered as a reference, or by 30.57% when Lira is considered as a reference.

Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice.

The objective of this article was to review pharmacology, efficacy, safety, and place in therapy of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. PubMed/MEDLINE and ClinicalTrials.gov were searched through September 7, 2022, using the keyword "tirzepatide." Clinical trials with available results were included. Seven published phase 3, multicenter, randomized, parallel-group trials investigated efficacy and safety of tirzepatide versus placebo, semaglutide, insulin degludec, and insulin glargine for type 2 diabetes mellitus (T2DM) treatment. Studies included adults with uncontrolled T2DM and body mass index above 23 or 25 kg/m2. Hemoglobin A1c reduction from baseline was greater with tirzepatide across all studies with absolute reductions up to 3.02% and relative reductions ranging 0.44% (vs semaglutide) to 2.11% (vs placebo). Weight loss was significant. Incidence of gastrointestinal adverse effects (AE) was similar to semaglutide, and major cardiovascular events was similar to insulin glargine. Studies demonstrated greater A1c lowering and weight reduction versus placebo and active comparators with AE similar to semaglutide, suggesting tirzepatide will be a valuable addition to the growing list of antidiabetic medications. Although tirzepatide's effects on major cardiovascular events was not increased when compared with insulin glargine, further evidence is needed to assess long-term implications on cardiovascular outcomes compared with agents with proven cardiovascular benefits. Tirzepatide has the potential to significantly impact the clinical management of T2DM, and results of ongoing clinical trials will help to fully determine its place in therapy.

Changes of HbA1c variability after the switch to a longer-acting insulin analog in people with type 1 diabetes.

This study investigated whether longer-acting basal analogs (insulin degludec and insulin glargine U300) could reduce visit-to-visit hemoglobin A1c (HbA1c) variability in patients with type 1 diabetes. Ninety adults with type 1 diabetes for whom the basal insulin was switched to a longer-acting insulin analog were analyzed retrospectively. The coefficient of variation of HbA1c levels (CV-HbA1c) during the year before and after the switch was compared. The CV-HbA1c after the switch was not significantly different from that before the switch (4.39 ± 2.24% vs 4.25 ± 2.07%; P=0.506). The linear regression model revealed that CV-HbA1c before the switch was independently associated with the change of CV-HbA1c (regression coefficient per standard deviation=-0.568, P < 0.001), whereas the other variables were not (all P > 0.05). In conclusion, CV-HbA1c remained unchanged after the switch on average, but CV-HbA1c before the switch was associated with the decrease of CV-HbA1c in individuals with type 1 diabetes.

Initiation of the Fixed Combination IDegLira in Patients with Type 2 Diabetes on Prior Injectable Therapy: Insights from the EASY French Real-World Study.

Combining basal insulin (BI) with glucagon-like peptide-1 receptor agonist (GLP-1RA) is recognized as a relevant option to optimize glucose control in type 2 diabetes (T2D). The EASY real-world study aimed to evaluate the modalities of initiation and the effectiveness of the insulin Degludec plus Liraglutide (IDegLira) fixed-ratio combination in the French health care system. A retrospective analysis included all patients with T2D and prior injectable therapy (GLP1-RA and/or insulin) who started treatment with IDegLira from September 2016 to December 2017 in 11 French diabetes centers. Baseline characteristics, reasons for IDegLira initiation, and modes of implementation were collected from the medical records. Changes in HbA1c and body weight were determined in patients with available follow-up data (nearest 6-month visit). IDegLira was initiated in 629 patients previously treated with GLP-1RA alone (11.6%), insulin alone (31.5% including 16.5% with BI and 14.9% with multiple daily injections [MDI]) or a free combination of GLP-1RA and insulin (56.9% including 44.8% with BI and 12.1% with MDI), associated or not with oral agents. IDegLira starting dose (mean of 29 ± 11 dose steps) most often exceeded the recommended dose, and was significantly correlated with prior BI but not GLP-1RA dosage. At initiation, mean age, body mass index (BMI) and HbA1c were 60.1 ± 10.2years, 33.4 ± 6.2kg/m2 and 8.8 ± 1.7%, respectively. In 461 patients with available follow-up (median 178days), HbA1c decreased in all subgroups submitted to treatment intensification (- 1.7 ± 1.8% [p < 0.0001], - 1.2 ± 1.8% [p < 0.001] and -0.8 ± 1.8% [p = 0.0026] in patients with prior GLP-1RA, BI or MDI therapy, respectively) but also in those switching from BI and GLP-1RA free combination (- 0.2 ± 0.9%, p = 0.0419). Significant body weight gain occurred in patients previously treated with GLP-1RA alone (+ 1.5 ± 5.8kg, p = 0.0572) or combined to BI (+ 1.0 ± 3.1kg, p < 0.0001) while those on BI (- 1.4 ± 4.6kg, p = 0.0139) or MDI (- 1.4 ± 5.0kg, p = 0.0484) experienced weight loss. While providing new information on the use of IDegLira in the French healthcare system, these data confirm the effectiveness of this fixed-ratio combination in the management of T2D.

OR03-1 Achievement of HbA1c &amp;lt;6.5% without weight gain and hypoglycemia in people with type 2 diabetes treated with tirzepatide across the phase 3 SURPASS program

Abstract Introduction Tirzepatide, the novel dual GIP/GLP-1 receptor agonist for the treatment of type 2 diabetes, has been shown to reduce HbA1c and weight, with more patients achieving HbA1c ≤6.5%, compared to placebo and active comparators in the phase 3 SURPASS 1-5 studies. This analysis compared the percentage of patients treated with tirzepatide achieving a composite endpoint of HbA1c &amp;lt;6.5% without weight gain and hypoglycemia in these studies. Methods We compared the proportion of participants achieving the composite endpoint between the tirzepatide (5, 10, or 15 mg) and respective comparator groups while patients were on treatment and without rescue medication. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. End of treatment HbA1c and weight were evaluated at week 40 (SURPASS-1, 2, 5) and week 52 (SURPASS-3, 4). Weight gain was defined as a change from baseline in weight &amp;lt;0.1 kg. Hypoglycemia included blood glucose level &amp;lt;54 mg/dL with symptoms of hypoglycemia or severe hypoglycemia. Results In SURPASS-1, 2, 3, 4, and 5 significantly more patients treated with tirzepatide achieved the composite endpoint compared to placebo or comparator (P≤0.002). As a monotherapy in SURPASS-1, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (75%, 78%, 83%, and 5%, respectively; all P&amp;lt;0.001). As add-on to metformin in SURPASS-2, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than semaglutide (67%, 77%, 83%, and 59%, respectively; P=0.002, P&amp;lt;0.001, P&amp;lt;0.001, respectively). When compared to basal insulin in SURPASS-3, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin degludec (63%, 76%, 82%, and 13%, respectively; all P&amp;lt;0.001). When added to 1-3 oral antihyperglycemics in SURPASS-4, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin glargine (56%, 68%, 75%, and 10%, respectively; all P&amp;lt;0.001). As an add-on to basal insulin in SURPASS-5, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (63%, 70%, 76%, and 8% respectively; all P&amp;lt;0.001). Conclusions Significantly more patients treated with tirzepatide achieved a composite endpoint of HbA1c &amp;lt;6.5% without weight gain or hypoglycemia than those treated with placebo, semaglutide, insulin degludec, or insulin glargine in the phase 3 SURPASS program. Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.

ODP255 Woman With Maturity-Onset Diabetes of the Young Type 2 (MODY2) Mistakenly Diagnosed and Treated as Type 2 Diabetes Mellitus

Abstract Background MODY2 is a rare, monogenic form of diabetes, caused by mutations in the glucokinase gene (GCK), and is often misclassified as type 2 diabetes. Clinical case: A 37-year-old woman, during childhood, at the age of 9, was characterized as overweight and had a poor diet, despite being physically active. Her pediatrician diagnosed her with DM2 and started treatment with metformin. However, there was no improvement in fasting glucose levels, so the family decided to stop the medication on their own. In 2008, the patient became pregnant, presenting fasting glucose levels between 120-130 mg/dl (n&amp;lt;99 mg/dl), and continued without hypoglycemic treatment. In 2010, she resumed treatment for glycemic control having used: metformin, sulphonylurea, IDDP4, and basal insulin. Despite the various treatments tested, there was altered fasting glycemia, in the 130mg/dl range. In 2012, she increased her physical activity by training for a half marathon run. At the peak of her form, but maintaining hyperglycemia (always measuring while fasting), she started liraglutide 1.8mg. In 2019, she presented episodes of malaise during training, being indicated by her physician, to discontinue liraglutide, then starting dapagliflozin, but there was still no improvement of blood glucose levels. In August 2019, she was instructed to take the following medications: insulin degludec, liraglutide, and dapagliflozin. Current weight was 53kg, height 1,57cm and a BMI 21,5kg/. Laboratory exams were requested with the following results: A1C 6,6% (n: &amp;lt;5,7%), mean glycemia 143mg/dL (n: 70-99 mg/dL), fasting glycemia 127mg/dL (n: &amp;lt;100mg/dL), urea 24mg/dL (n: 13-43 mg/dL), creatinine 0,83mg/dL (n: 0,8-1,3 mg/dL), AST 16U/L (n: 10-34 U/L), ALT 17U/L (n 10-130 U/L), LDL 109mg/dL (n&amp;lt;100mg/dl), HDL 80mg/dL (n&amp;gt;60 mg/dL), TG 90mg/dL (n&amp;lt;150 mg/dL), total cholesterol 207mg/dL (&amp;lt;200 mg/dL). Faced with the suspicion of diabetes with different behavior than DM1 and DM2, genetic testing was requested for confirmation. In September 2019, the result arrived, pointing out a genetic change in heterozygosis in the GCK gene. This is a rare mutation that results in the depletion of the phenylalanine amino acid at position 150 of the protein glucokinase. This result confirmed the diagnose of MODY type 2. The patient was oriented to discontinue anti-hyperglycemic agents, maintain a low glycemic index diet, and daily physical exercises. Thus, she has been maintaining excellent glycemic control and adequate weight. Conclusion Suspicion and characterization of MODY through clinical history, and confirmation of diagnosis through genetic testing, is essential to avoid unnecessary or inefficient treatments, and to ensure a better quality of life for the patient. Presentation: No date and time listed

ODP167 Bell's Palsy As A Possible Post-Covid-19 Complication In Patient With Type 2 Diabetes

Abstract Background Diabetes is associated with increased risk of post COVID-19 infection complications which has been postulated to be due to uncontrolled carbohydrate, fat metabolism and raised insulin resistance. Bell's palsy (BP) is an idiopathic unilateral facial paralysis that constitutes the most common cause immune response after a viral infection. Clinical Case A 48- years-old male with type 2 diabetes (BMI-35,3 kg/m 2,HbA1C- 7.6%). He was on regular treatment with metformin(daily doses (DD)– 1500 mg)for the last five years. Before 4 months for hospitalization in the patient was positive nasopharyngeal polymerase chain reaction (PCR) test for SARS-CoV-2 and he didn't develop clinical symptoms of COVID-19, that confirmed asymptomatic coronavirus disease. The male had no history of trauma or systemic infection, and presented no skin eruptions compatible with herpes zoster infection. There were asymmetric wrinkling of the forehead inability to raise the right eyebrow, failure to close the right eyelid, and right deviation of the angle of the mouth (right-sided droop), suggesting right seventh cranial nerve palsy of lower motor neuron type. Signs of meningeal irritations were absent. The neurologist confirmed the diagnosis of right unilateral BP. On hospital stay the patient was treated: metformin (DD – 2000 mg), dapagliflozin (DD – 10 mg), and subcutaneous insulin degludec (DD – 22 units); oral prednisolone at 40 mg/day for one week, which was subsequently tapered to 35 mg/day for 7 days and 30 mg/day for the next 7 days, with a total of 2 months of treatment and assigned to 15 sessions of acupuncture treatments during 10 minutes 5 times/week. The result discussion of clinical studies that diabetes was not a poor prognostic indicator if treated with corticosteroids in diabetic BP patients. Facial palsy started improving after 15 days of admission, and throat swab PCR for SARS-CoV-2 came negative during hospitalization. He was discharged on the 23th day of admission. After3 months, the treating team contacted the patient by phone and realized that he was in good condition, and his facial weakness had improved significantly. However, there are still some residual weaknesses. The sixth months therapy resulted in patient's recovery functions of right seventh cranial nerve and compensation of type 2 diabetes was achieved (HbA1C-7. 0%). Conclusion We assume that our patient got BP secondary to post-COVID-19 complication. These findings support the use of corticosteroids and sessions of acupuncture when necessary for treatment of post-COVID-19 neurological complications in subjects with diabetes. We believe that further research should be conducted to clarify the pathogenic association between COVID-19 and BP in patients with type 2 diabetes and improve algorithm of treatment. Presentation: No date and time listed

LBSUN291 Fournier's Gangrene In A Diabetic Male Taking Dapagliflozin

Abstract Background Fournier's gangrene (FG) is a form of necrotizing fasciitis characterized by polymicrobial infection of the perineal, perianal or genital areas; risk factors include diabetes mellitus and male gender. Dapagliflozin is one of four sodium-glucose cotransporter 2 (SGLT2) inhibitors FDA-approved for the treatment of Type 2 diabetes mellitus (T2DM). SGLT2 inhibitors decrease serum glucose and increase glycosuria by binding to renal tubular SGLT2 receptors, and inhibiting reabsorption of glucose from urine in the proximal convoluted tubule. Since their introduction in 2013, SGLT2 inhibitors have been shown to protect against decline in GFR, to improve LVEF in HFrEF, and to improve survival in T2DM. However, due to associated glycosuria, SGLT2 inhibitors are commonly associated with candidiasis, and are rarely associated with life-threatening adverse effects including FG, and euglycemic diabetic ketoacidosis. | Clinical case: A 57-year-old male with T2DM, diabetic neuropathy and hypertension presented to the ED with left testicular swelling, penile discharge and dysuria of several days duration. He was afebrile and vital signs were in normal ranges. Examination disclosed left-sided scrotal swelling surrounding a 1 cm black eschar, induration, erythema and discharge. WBC 15.1 with 79% neutrophils and HbA1c 10.4%. Dapagliflozin 4 mg daily had been added to insulin degludec one month earlier. He denied previous history of scrotal/genital infections. Ultrasound of the scrotum showed wall thickening on the left, a small hydrocele and heterogenous echogenicity suggesting an abscess. Pelvic CT scan with contrast revealed multiple small air bubbles in the scrotal wall. Findings were consistent with FG. He was treated promptly with IV piperacillin / tazobactam and vancomycin. Urological debridement of necrotic scrotal skin was carried out the morning after admission; cultures obtained at surgery grew Gram neg rods and Diphtheroids. Tissues within the scrotum were not gangrenous. Primary closure with a Penrose drain was attempted, but the skin surrounding the sutures necrosed and a second urological procedure was done to remove the sutures and allow the scrotal wall to heal by secondary intention. He was discharged after 5 days and I. V. ampicillin/sulbactam was continued for a total of 14 days with resolution of infection and healing of the skin. Conclusion SGLT2 inhibitors decrease mortality and increase quality of life in T2DM compared to older treatments with exogenous insulin and its secretagogues. Optimal utilization of SGLT2 inhibitors in the management of patients with T2DM will entail 1) quantifying risk specifically attributable to SGLT2 inhibitors since T2DM is a known risk factor for FG, and 2) routinely informing/reminding patients with T2DM to promptly report skin infections of the groin, perineum or perianal region. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSUN247 Unique Presentation of MODY Type 5

Abstract A 46-year-old female with a past medical history significant for a blind vaginal birth defect that required vaginal reconstructive surgery with a partial hysterectomy at 15 years old and Type 2 Diabetes diagnosed at 44 years old. The patient was started on Sitagliptin, metformin 500 mg BID, and glimepiride 2 mg, but she remained poorly controlled with A1C 12.5%. Liver enzymes were elevated with the following values on the liver panel: AST 63 U/L Alt113 U/L bilirubin total 1.0 U/L direct bilirubin 0.3 U/L Alkaline phosphatase 642 U/L. Abdominal ultrasound and serology for chronic liver disease were unremarkable; enhanced MRI of the abdomen showed no abnormalities in the liver and pancreas. CT-guided liver biopsy was performed and pathology revealed diabetic hepatosclerosis. Ultimately, the patient was referred for endocrinology evaluation for poorly controlled diabetes mellites. Blood work was negative for GAD antibodies 65 and anti-pancreatic islet cell antibodies. C peptide level was within normal limits. The patient was not compliant with medications; her A1C continues to range between 11.5 and 8.5 so she was started on subcutaneous insulin. A few years later, the patient presented to the ED for generalized weakness, anorexia, and unintentional weight loss of approximately 40 pounds with a BMI of 17 kg/m2. Bloodwork revealed glucose was 222 mg/dl, and glycated hemoglobin (A1C) was 15.4%, with no acute metabolic disorder (no ketosis). Biochemical analysis reported triglycerides of 174 mg/dL, total cholesterol of 280 mg/dL, HDL of 82 mg/dL, aspartate aminotransferase of 75 U/L, alanine aminotransferase of 117 U/L. alkaline phosphatases 190U/L, Potassium 3.1mEq/L, and magnesium 1.3mEq/L Her electrolytes failed to correct despite adequate replacement; hence nephrology evaluation was warranted. As a result, 24h urine collection was obtained and revealed a Gitelman pattern with salt wasting, K+ wasting, Mg2+ wasting, and no calcinuria. This raised suspicion for MODY type 5. An enhanced MRI of the abdomen revealed her pancreas was missing the distal body and tail as well as bilateral cystic kidney disease. Genetic testing was pursued and demonstrated mutations in the hepatic nuclear factor 1B (HNF1B) gene which confirmed the MODY type 5 diagnosis. The patient was discharged on 11 units of insulin degludec at bedtime in addition to insulin aspart 2 units TID; her A1c improved to 8.3% on her most recent follow-up. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Demographic and clinical characteristics of a Spanish population of people living with type 1 diabetes who practice nonprofessional sports: The DIABESPORT survey

AimTo determine the characteristics of people with type 1 diabetes mellitus (T1D) who practice sports, the support they receive, and the way in which they manage their disease during sports. MethodsAn observational cross-sectional study designed as a web-based survey released through social media was carried out, directed to physically active people with T1D. ResultsA total of 342 subjects completed the survey (16 children; 67.5% males). The duration of living with T1D was 18.6 ± 11.4 years. The mean glycosylated hemoglobin concentration (HbA1c) was 6.7 ± 0.8%, and the mean time in range (TIR) was 72.9 ± 15.8%. Only 27.2% started sports activity following the diagnosis of T1D. The most frequently used basal insulin was insulin degludec (38.6%). The usual treatment modification before doing sports consisted of bolus reduction (42.5%) or only the adjustment of nutritional supplements (19.7%). In cases of long-acting insulin users, the basal dose usually remained unchanged during sports. One-quarter of the participants were insulin pump users, and of these, 12.5% always disconnected the pump during physical activities. Severe hypoglycemia on the day of physical activity was experienced by 5% of the participants in the last 6 months. One-third reported a lack of support from their physician, and 61% had learned to manage glycemic control during sports by themselves. ConclusionsThis study highlights the adjustments made by people living with T1D during sports practice, and the lack of support received from healthcare professionals.

Efficacy and Tolerability of Insulin Degludec Versus Other Long-acting Basal Insulin Analogues in the Treatment of Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

PurposeThe goal of this study was to compare the efficacy and tolerability of insulin degludec with those of other long-acting insulin analogues (insulin glargine and insulin detemir) in patients with type 1 or 2 diabetes mellitus (T1D or T2D). MethodsThose randomized controlled trials comparing insulin degludec with other long-acting insulin analogues in the treatment of patients with T1D or T2D published on or before August 21, 2022, were retrieved from PubMed, Web of Science, the Cochrane Library, and EMBASE. The efficacy end points were the changes from baseline in hemoglobin A1c and fasting plasma glucose (FPG). The tolerability end point was the prevalence of hypoglycemia confirmed throughout the treatment period. FindingsData from a total of 20 trials (19,048 patients) were included. The differences in the reductions in glycosylated hemoglobin between insulin degludec and other long-acting basal insulin analogues (insulin glargine and insulin detemir) used for the treatment of patients with T1D or T2D were not significant. However, the reduction in FPG was greater with insulin degludec (–0.370 mmol/L; 95% CI, –0.473 to –0.267 mmol/L; P ≤ 0.001). Throughout the treatment periods of all of the available trials, the estimated rate ratios of overall and nocturnal hypoglycemia were significantly decreased with insulin degludec compared with insulin glargine or insulin detemir in patients with T1D or T2D; the differences in the risks for severe hypoglycemia were not significant. ImplicationsCompared with other long-acting insulin analogues (insulin glargine and insulin detemir), insulin degludec was associated with a significantly decreased FPG, with lower prevalences of overall and nocturnal hypoglycemia.

Who are the Best Candidate Patients with Diabetes for Tirzepatide?

Background: Tirzepatide is a dual receptor agonist of the 2 incretin hormones: Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon- Like Peptide-1 (GLP-1) which is was recently approved for treatment of type 2 diabetes. Objective: To define the most appropriate patients that may benefit from tirzepatide. Methods: Pubmed search until August 10, 2022. Search terms were GLP- 1, GIP, tirzepatide, efficacy, safety, obesity. Clinical trials and pertinent animal studies and reviews were included. Results: Tirzepatide was more effective in lowering hemoglobin A1c (HbA1c) levels and body weight than submaximal doses of semaglutide (1.0 mg once-weekly), dulaglutide (1.5 mg once-weekly), insulin degludec (mean daily dose 48.8 U) and insulin glargine (mean daily dose 43.5 U). In patients with type 2 diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD), tirzepatide significantly decreased Liver Fat Content (LVC). Safety profile of tirzepatide was generally similar to that of GLP-1 agonists, but frequency of Gastrointestinal (GI) adverse effects are slightly higher with tirzepatide. Incidence of severe hypoglycemia (blood glucose &lt; 54 mg/dl) is also slightly higher with tirzepatide than semaglutide and dulaglutide, but much lower than insulin degludec and glargine. Drug discontinuation rates due to adverse effects were higher with tirzepatide compared with semaglutide, dulaglutide, and insulin. Conclusions: Tirzepatide may be most appropriate for patients with type 2 diabetes who are obese, as alternative to GLP-1 agonists or basal insulin, and in patients with NAFLD.

Real-world effectiveness of IDegLira compared with intensified conventional insulin therapy in adults with type 2 diabetes: a retrospective cohort study

BackgroundIDegLira is a fixed-ratio combination of insulin degludec and liraglutide with proven efficacy against simpler regimens and non-inferiority against basal-bolus insulin therapy. However, the evaluation of its real-world effectiveness is hindered by technical issues and requires further exploration. Thus we aimed to compare effectiveness of insulin degludec/liraglutide (IDegLira) versus intensified conventional insulin therapy (ICT) for type 2 diabetes in a real-world setting.MethodsThis retrospective cohort study from an outpatient clinic in Hungary included people who initiated IDegLira due to inadequate glycaemic control (HbA1c > 7.0% [53.0 mmol/mol]) with oral and/or injectable antidiabetic drugs. Data were compared with a historical cohort who initiated ICT. Outcomes included HbA1c, body weight, and hypoglycaemia differences over 18 months of follow-up.ResultsData were included from 227 and 72 people who initiated IDegLira and ICT, respectively. Estimated mean difference (MD) in HbA1c at 18 months favoured IDegLira versus ICT (MD 0.60, 95% CI 0.88–0.32 [MD 6.6 mmol/mol, 95% CI 9.6–3.5]). More people reached target HbA1c ≤7.0% (53.0 mmol/mol) with IDegLira than ICT (odds ratio 3.36, 95% CI 1.52–7.42). IDegLira treatment was associated with weight loss compared with gain for ICT (MD 6.7 kg, 95% CI 5.0–8.5). The hazard ratio for hypoglycaemia comparing IDegLira with ICT was 0.18 (95% CI 0.08–0.49).ConclusionsTreatment with IDegLira over 18 months resulted in greater HbA1c reductions, weight loss versus gain, and a lower rate of hypoglycaemia versus ICT in people with type 2 diabetes.

Effect of fixed-dose combination of insulin degludec and liraglutide on apoB-containing lipoprotein subclasses and HDL lipidome in type 2 diabetes

AimsAdministration of insulin degludec and liraglutide (IDegLira) correlates to fasting lipid profile changes of diabetic patients, while data concerning apoB-containing lipoprotein subclasses and HDL lipidome are scarce. We evaluated its effect on fasting lipid parameters, apolipoproteins, apoB-containing lipoprotein subclasses and HDL lipidome in patients with type 2 diabetes. MethodsSixty three patients with HbA1c > 7 % on oral glucose-lowering drugs received either IDegLira or insulin degludec for 3 months. Lipoprotein subfraction profile was determined through Lipoprint method, whereas HDL lipid composition via 1H NMR. ResultsCompared to insulin degludec, IDegLira administration resulted in significantly greater reduction of total and LDL-cholesterol. On the other hand, the effect of the two drugs on apolipoprotein-B-containing lipoprotein subfractions concentration was minimal and did not differ between the 2 interventions. IDegLira, but not insulin degludec, induced an atheroprotective shift in HDL's fatty acid composition and particle core depletion in triglycerides. ConclusionsIDegLira administration is accompanied by total and LDL-cholesterol reduction, while sdLDL concentration only reduced in patients experiencing triglyceride reduction. IDegLira induced compositional changes of HDL particles. These changes may contribute to the cardioprotective properties of liraglutide.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with insulin glargine/degludec in adults with type 2 diabetes: a prospective, randomized, double-blind, phase 3 trial

Ultra rapid lispro (URLi) is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal, with the aim of improving postprandial glucose (PPG) control. We conducted a multinational, multicenter, randomized, double-blind, treat-to-target, 26-week, phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes (T2D). After an 8-week lead-in period during which basal insulin glargine or degludec was optimized, adults with T2D were randomized (2:1) to prandial URLi (n = 395) or lispro (n = 200). The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c (HbA1c) change from baseline to week 26. Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1- and 2-h PPG excursions during a mixed-meal tolerance test (MMTT) and HbA1c change at week 26. URLi showed non-inferiority for HbA1c change at week 26 versus lispro (least-squares mean [LSM] difference, 0.07%; 95% confidence interval: −0.07, 0.21). HbA1c was reduced by 0.56% and 0.63% with URLi and lispro, respectively, with no significant treatment difference (P = 0.321). URLi provided superior PPG excursion control versus lispro at 1 h (LSM difference: −14.6 mg/dL, P < 0.001) and 2 h (LSM difference: −21.8 mg/dL, P < 0.001) as well as other time points (30–240 min) during the MMTT. Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro. The safety profiles were generally similar between treatment groups. In conclusion, URLi was superior to lispro for PPG control, with non-inferiority in HbA1c improvement, in adults with T2D.

Discovery of Insulin/GLP-1/Glucagon Triagonists for the Treatment of Diabetes and Obesity.

The combination of insulin and incretin-based therapies has emerged as a potential promising tactic for the treatment of diabetes. Here we report the first example of a unimolecular triagonist to simultaneously target insulin, GLP-1, and glucagon receptors, aiming for better glycemic control and superior weight loss. The strategy for constructing such a unimolecular triagonist is the conjugation of the insulin moiety and GLP-1R/GCGR coagonist peptide via alkyne-azide click chemistry. Two tractable series differentiated by insulin conjugation sites, B1F and B29K, were identified. Triagonist 13 prepared through the conjugation at insulin B1F and position 24 of GLP-1R/GCGR coagonist exhibited insulin activity comparable to that of insulin degludec and potent and balanced GLP-1R and GCGR activities. Pharmacokinetic profiles of 13 in both rat and minipig were also discussed.